Overview

The primary pathologic or structural change observed in patients with atrial fibrillation is progressive fibrosis of the atria. This fibrosis is primarily due to atrial dilatation, however genetic causes and inflammation may also play a role in some individuals. There are other functional processes that contribute to the development and persistence of atrial fibrillation including hemodynamic stress (stretching of the atrium), atrial ischemia, activation of the neurohormonal system, ectopic activity in the pulmonary vein, multiple wavelets of electrical activity in the atrium, and catecholamine excess. The mechanism in most patients is likely to be multifactorial.

Pathophysiology

Triggers

Onset of atrial fibrillation is dependent upon specific triggers and tissue substrate capable of maintaining atrial fibrillation. The following triggers are know to initiate atrial fibrillation:[1]

Ectopic Foci in the Pulmonary Vein

Younger patients with paroxysmal atrial fibrillation will sometimes have ectopic foci of electrical activity in the pulmonary vein that can be ablated. There are cells in the pulmonary vein whose electrical properties resemble those of the myocytes of the atrium. These patients generally have high grade ectopic activity on Holter monitoring. While the pulmonary vein is a common source of these ectopic foci, there may also be foci present in the atrium itself. While the pulmonary vein may function as a trigger, it is the heterogeneity of conduction that may sustain the atrial fibrillation

Re-enterant Wavelets or Multiple Wavelets Phenomenon

Presence of these triggers produce re-enterant wavelets of electrical activity due to shortened effective refractory period (ERP)

It has been hypothesized that if there is a greater atrial mass, delayed atrial conduction times, and a shortened atrialrefractory period, it promotes the propagation of wavelets.[2] This hypothesis is supported by the observation that prolongation of intra atrial conduction times is associated with a recurrence of atrial fibrillation.

Molecular Pathogenesis and Role of Mechano-electric Feedback

Mechanosensitivity of cardiacmyocytes is thought to play a pivotal role in initiation of atrial fibrillation:[3]

Animal studies have shown that the gap junction protein connexin 43 (Cx43) plays a key role in electrical conduction velocity in cardiac tissues, and under expression of Cx43 is linked with AF(especially in sympathetic AF).[7][8]

Once dilatation of the atria has occurred, this begins a chain of events that leads to the activation of the renin aldosterone angiotensin system (RAAS) and subsequent increase in matrix metaloproteinases and disintegrin, which leads to atrial remodeling and fibrosis, with loss of atrial muscle mass.

Dilation and stress may lead to decreased resting potential, action potential amplitude and duration, and occurrence of afterdepolarizations causing extrasystoles.